We have been developing strategies to utilize nitric oxide (NO) in cancer treatment. In addition to the use of synthetic NO donors, we are researching the mechanisms that control the endogenous cellular production. We have recently discovered that inhibition of Nitric oxide synthase (NOS) given after chemotherapy or radiation treatment enhances tumor re-growth delay. Given that there are a number of clinically available NOS inhibitors this could have potential clinical applications. We have recently characterized the NO levels that are required to activate and stabilize key proteins involved in carcinogenesis, p53, ERK and HIF. We have extended this work to show that levels of NO are criical to angiogenesis and that NO and TSP-1 regulate each other pathways. We have shown that the proangiogenic mechanisms of NO is abated by TSP-1 and that the transcription of the antiangiogenic agent TSP-1 was inhibited by NO. This seminal finding sheds light on the potential mechanism of the tumor re-growth delay by NOS inhibitors. We have also been examining the physiological effects of nitroxyl (HNO/NO-) a redox sibling of NO. We have found it to be valuable in the treatment of heart failure, precondition organs against ischemia reperfusion and a selective COX-2 inhibitor. We have recently developed new compounds that can be modified to deliver nitroxyl in vivo. In addition, we have established an HPLC method for specific detection of NO from chemical or biochemical sources.